Thioterpenoids as Potential Antithrombotic Drugs: Molecular Docking, Antiaggregant, Anticoagulant and Antioxidant Activities

Abstract

Natural monoterpenes and their derivatives are widely considered as effective ingredients for the design and production of new biologically active compounds with high antioxidant, antimicrobial and anti-protozoa properties. In this study, we synthesized two series of thiotherpenoids “sulfide-sulfoxide-sulfone”, with different bicyclic monoterpene skeleton (bornane and pinane) structures. The effect of the obtained compounds on platelet aggregation was investigated by using the molecular docking technique. The obtained data revealed that all the synthesized compounds may act as potential inhibitors of platelet aggregation. Moreover, the studied sulfides have shown high antioxidant activity as revealed by lipid peroxidation (LPO) process inhibition in a non-cellular substrate containing animal lipids. The sulfides were able to inhibit erythrocyte oxidative hemolysis, to reduce the accumulation of secondary LPO products in cells and to prevent the oxidation of native oxyhemoglobin. Additionally, the corresponding sulfones and sulfoxides exhibited insignificant antioxidant activity. However, the sulfides were found to exhibit significant antiaggregant and anticoagulant effects. These findings suggest as well that the sulfides could serve as a leader compound for future research and possible practical applications.

In Vitro Screening of Antimicrobial and Anti-Coagulant Activities, ADME Profiling, and Molecular Docking Study of Citrus limon L. and Citrus paradisi L. Cold-Pressed Volatile Oils

“…Previous reports have shown that monoterpenes exhibit anticoagulant activities by affecting the hemostasis process. They can reduce collagen-induced platelet aggregation, induce antithrombotic reactions and block the P2Y12 platelet receptor [46,47]. Citrus caused the inactivation of thrombin and a decrease in the concentration of fibrinogen.…”

Unraveling the Mechanism of Platelet Aggregation Suppression by Thioterpenoids: Molecular Docking and In Vivo Antiaggregant Activity

“…In our previous work, two series of "sulfide-sulfoxide-sulfone" thioterpenoids, differing from each other in the structure of their terpenic skeletons, have been described [9]. The obtained compounds, 1-3, present bornane series compounds; meanwhile, compounds 4-6 present the pinane series (Figure 1).…”